A Pharmaco-imaging Approach to Predicting Social Functioning and Clinical Responses to Oxytocin Administration in Schizophrenia

Schizophrenia has a devastating and disproportionate effect on veterans compared to the general US population. Some of the most disabling symptoms, such as low motivation, difficulty expressing emotions, and decreased ability to infer the mental states of others, cause poor social functioning. This means that veterans with schizophrenia have trouble navigating interpersonal interactions and building meaningful relationships in the community. Unfortunately, current antipsychotic medications typically only improve positive symptoms but fail to improve social functioning deficits, which are strong predictors of poor quality of life and functional outcomes. Oxytocin, a peptide found in the brain, plays an important role in social behavior and is known to moderate affiliation, stress, and learning across taxa. In this study, the investigators will test whether oxytocin could be an effective treatment for social functioning deficits in schizophrenia. The investigators will examine changes in brain activation to understand how oxytocin affects behavior and to predict which individuals may benefit from oxytocin treatment.

Study Overview

• Status: Terminated
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Placebo; Drug: Oxytocin

Detailed Description

The study uses a combined within- and between-subject placebo-controlled study design. After screening, participants will be randomized into two study arms for the fMRI phase of the study. In each study arm, participants will complete a placebo-controlled, within-subject, pharmaco-fMRI paradigm with one of two possible dosages of oxytocin (20 or 40IU) and placebo. In the fMRI scanner, they will complete two well-validated theory of mind tasks: the false belief task and the person description task. Following the fMRI phase of the study, participants will be randomized to receive the same dosage of oxytocin the participant received in the fMRI phase, or placebo, twice daily for 3 weeks. Before and after the three weeks of drug administration, participants will be assessed for social functioning, social ability, negative symptoms, and theory of mind. More participants will be randomized to receive chronically administered oxytocin than placebo to maximize the study's power to test the investigators' hypothesis that acute oxytocin-induced increases in right temporo-parietal junction activity will be positively correlated with improvements in social functioning (primary outcome), social ability, negative symptoms, and theory of mind over three weeks of oxytocin administration.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Josh Woolley, BS; Phone Number: 4117 (415) 221-4810; Email: Josh.Woolley@ucsf.edu
• Study Contact Backup: Name: Jake C Gibson, BA; Phone Number: 24117 (415) 221-4810

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94121-1563
      • San Francisco VA Medical Center, San Francisco, CA
    • West Los Angeles, California, United States, 90073
      • VA Greater Los Angeles Healthcare System, West Los Angeles, CA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Veteran
• age 18-70
• a diagnosis of schizophrenia, schizophreniform, schizoaffective, or brief psychotic disorder determined by the Structured Clinical Interview for DSM-5
• no medication changes or psychiatric hospitalizations in the past month
• SFS modified raw score of no more than 75

Exclusion Criteria:

• substance use disorder in the past month, except mild to moderate cannabis use disorder
• illness affecting the nasal passages
• significant neurological/medical disorder
• pacemakers
• extensive dental work
• claustrophobia
• deafness
• inability to read
• currently participating in a psychosocial intervention targeting social functioning deficits
• currently taking high dose testosterone or estrogen/progesterone
• inability to complete VOT

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Saline	Drug: Placebo; Placebo
Experimental: Intranasal Oxytocin; Dosages of oxytocin: 20IU or 40IU.	Drug: Oxytocin; Intranasal administration of oxytocin; Other Names: Syntocinon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Social Functioning Score	The Social Functioning Scale is a 79-item semi-structured interview based assessment that includes [a global summary score (primary outcome) as well as seven subscales (secondary outcomes): social engagement, interpersonal communication, independence, competence, recreation, prosocial, and employment.] A mean of the subscale scores provides overall score of social functioning. Each subscale score is transformed into a standard distribution with a mean of 100 and standard deviation of 15 for comparability and interpretation. Higher scores indicates a high level of functioning.	From the baseline visit in the chronic OT administration portion of the study design to after three weeks of oxytocin administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CAINS Score (clinical assessment interview for negative symptoms)	Negative symptoms will be assessed with the CAINS, comprising two subscales reflecting the negative symptom factors: The 9-item Motivation and Pleasure subscale (each item is scored from 0 no impairments to 4 severe deficit) captures experiential negative symptoms by assessing motivation, behavior, and pleasure derived from social, vocational, and recreational activities over the past week. The MAP total score therefore ranges from 0-36. The 4-item Expression subscale (each item is scored from 0 no impairment to 4 severe deficit) captures both non-verbal (face, posture) and verbal expressivity (output, prosody). The EXP total score ranges from 0 to 16 (higher scores indicate greater severity of symptoms). The CAINS has excellent convergent and divergent validity.	From the baseline visit in the chronic OT administration portion of the study design to after three weeks of oxytocin administration

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
QLS Scale (quality of life)	Quality of Life will be assessed with the Quality of Life Scale (QLS), a 9-item assessment that measures domains such as interpersonal relations, occupation role functioning, and intrapsychic foundations. Each item is rated from 0 to 6 with the lower values indicating greater severity of symptoms. As such, the total score ranges from 0-54 (higher scores indicate good quality of life).	From the baseline visit in the chronic OT administration portion of the study design to after three weeks of oxytocin administration
Hinting Task	Theory of Mind (ToM) will be assessed using The Hinting Task, a well-validated tool where participants make social inferences after hearing 10 fictional conversations. Each conversation ends with one character's utterance and the participant is asked to determine its meaning.	From the baseline visit in the chronic OT administration portion of the study design to after three weeks of oxytocin administration

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Collaborators: University of California, San Francisco; VA Greater Los Angeles Healthcare System
• Investigators: Principal Investigator: Josh Woolley, BS, San Francisco VA Medical Center, San Francisco, CA

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2020
• Primary Completion (Actual): January 31, 2024
• Study Completion (Actual): January 31, 2024

Study Registration Dates

• First Submitted: April 1, 2019
• First Submitted That Met QC Criteria: April 2, 2019
• First Posted (Actual): April 3, 2019

Study Record Updates

• Last Update Posted (Estimated): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Oxytocin
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: MHBB-011-18F; 19-27265 (Other Identifier: University of California, San Francisco); 1I01CX001761-01A2 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Study Data/Documents

1. Informed Consent Form

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No